Global ETD Search

41	Planning for success: constructing a first responder planning methodology for homeland security Jankowski, Thaddeus K., Sr. 03 1900 (has links) CHDS State/Local / Approved for public release, distribution is unlimited / The planning methodologies used today by most U.S. fire departments are excellent for traditional missions, but wholly inadequate for the threats posed by terrorism. Planning in the fire service and the rest of the first responder community historically has relied on a one-dimensional approach that uses a scenario-based planning (SBP) methodology. This thesis argues that the fire service and others in the first responder community will be able to contribute to homeland security missions much more effectively, and efficiently, by switching to specially adapted versions of capabilities-based planning. This thesis proposes a new integrated planning methodology that combines the planning strengths of scenariobased planning, threat-based planning, and capabilities-based planning. The new method identifies capabilities that could be used to manage and mitigate the consequences of the different types of contingencies within the various response spectrums. It allows an organization to perform analysis and efficiency studies to evaluate the different spectrums of contingencies against existing capabilities and create a menu of capabilities necessary for the first responder to respond to all its missions, including immediate threats and terrorism, in the most efficient and cost-effective manner. / Battalion Chief, Fire Department City of New York National security United States Terrorism Prevention Planning Civil defense Fire service First responder community Planning methodology Scenario-based planning (SBP) Threat-based planning (TBP) Capabilities-based planning (CBP) Traditional response Immediate threats Homeland security missions Contingency spectrums
42	Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells Shakibaei, M., Buhrmann, C., Mobasheri, A. January 2011 (has links) No / Resveratrol is a polyphenolic phytoestrogen that has been shown to exhibit potent anti-oxidant, anti-inflammatory, and anti-catabolic properties. Increased osteoclastic and decreased osteoblastic activities result in bone resorption and loss of bone mass. These changes have been implicated in pathological processes in rheumatoid arthritis and osteoporosis. Receptor activator of NF-kappaB ligand (RANKL), a member of the TNF superfamily, is a major mediator of bone loss. In this study, we investigated the effects of resveratrol on RANKL during bone morphogenesis in high density bone cultures in vitro. Untreated bone-derived cell cultures produced well organized bone-like structures with a bone-specific matrix. Treatment with RANKL induced formation of tartrate-resistant acid phosphatase-positive multinucleated cells that exhibited morphological features of osteoclasts. RANKL induced NF-kappaB activation, whereas pretreatment with resveratrol completely inhibited this activation and suppressed the activation of IkappaBalpha kinase and IkappaBalpha phosphorylation and degradation. RANKL up-regulated p300 (a histone acetyltransferase) expression, which, in turn, promoted acetylation of NF-kappaB. Resveratrol inhibited RANKL-induced acetylation and nuclear translocation of NF-kappaB in a time- and concentration-dependent manner. In addition, activation of Sirt-1 (a histone deacetylase) by resveratrol induced Sirt-1-p300 association in bone-derived and preosteoblastic cells, leading to deacetylation of RANKL-induced NF-kappaB, inhibition of NF-kappaB transcriptional activation, and osteoclastogenesis. Co-treatment with resveratrol activated the bone transcription factors Cbfa-1 and Sirt-1 and induced the formation of Sirt-1-Cbfa-1 complexes. Overall, these results demonstrate that resveratrol-activated Sirt-1 plays pivotal roles in regulating the balance between the osteoclastic versus osteoblastic activity result in bone formation in vitro thereby highlighting its therapeutic potential for treating osteoporosis and rheumatoid arthritis-related bone loss. Animals Bone marrow cells Metabolism Cell line Core binding factor Alpha 1 subunit Genetics Dogs Enzyme inhibitors Pharmacology Humans Mice Multiprotein complexes NF-kappa B Osteoclasts Osteoporosis Drug therapy RANK Ligand Rheumatic fever Signal transduction Drug effects Sirtuin 1 Stilbenes Up-regulation p300-CBP transcription factors REF 2014
43	Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage Salem, Mohamed M.A., Shalbaf, Mohammad, Gibbons, Nick C., Chavan, Bhavan, Thornton, M. Julie, Schallreuter, Karin U. January 2009 (has links) No / Vitiligo is characterized by a patchy loss of inherited skin color affecting approximately 0.5% of individuals of all races. Despite the absence of the protecting pigment and the overwhelming evidence for hydrogen peroxide (H(2)O(2))-induced oxidative stress in the entire epidermis of these patients, there is neither increased photodamage/skin aging nor a higher incidence for sun-induced nonmelanoma skin cancer. Here we demonstrate for the first time increased DNA damage via 8-oxoguanine in the skin and plasma in association with epidermal up-regulated phosphorylated/acetylated p53 and high levels of the p53 antagonist p76(MDM2). Short-patch base-excision repair via hOgg1, APE1, and polymerasebeta DNA repair is up-regulated. Overexpression of Bcl-2 and low caspase 3 and cytochrome c levels argue against increased apoptosis in this disease. Moreover, we show the presence of high epidermal peroxynitrite (ONOO(-)) levels via nitrotyrosine together with high nitrated p53 levels. We demonstrate by EMSA that nitration of p53 by ONOO(-) (300 x 10(-6) M) abrogates DNA binding, while H(2)O(2)-oxidized p53 (10(-3) M) enhances DNA binding capacity and prevents ONOO(-)-induced abrogation of DNA binding. Taken together, we add a novel reactive oxygen species to the list of oxidative stress inducers in vitiligo. Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo. Adult Apoptosis Physiology Ataxia Telangiectasia Mutated Proteins Caspase 3 Biosynthesis Cell cycle proteins Metabolism Cytochromes c DNA DNA damage Drug effects DNA repair DNA-binding proteins Electrophoretic mobility shift assay Epidermis Guanosine Analogs & derivatives Humans Hydrogen peroxide Pharmacology Middle aged Oxidation-reduction Oxidative stress Peroxynitrous acid Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-mdm2 Tumor Suppressor Protein p53 Tumor Suppressor Proteins Up-Regulation Vitiligo p300-CBP Transcription Factors REF 2014

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